FTY-720 pre-treatment attenuates acute lung injury following bilateral renal ischemia/reperfusion but not bilateral nephrectomy

Acute kidney injury (AKI) frequently coexists with acute lung injury (ALI) in critically ill patients, resulting in high mortality rates in intensive care units. This study aimed to investigate the role of lymphocytes in ALI following bilateral renal ischemia and bilateral nephrectomy, using FTY-720 (Fingolimod), which inhibits lymphocyte release into the circulation. The study was conducted on 75 male Sprague-Dawley rats, which were divided into five groups: three untreated groups subjected to bilateral renal ischemia/reperfusion (BIR), bilateral nephrectomy (BNX), or a sham operation, and two groups pre-treated with FTY-720 followed by either BIR (BIR + FTY) or BNX (BNX + FTY). One hour of bilateral renal ischemia followed by 24 h of reperfusion caused severe kidney tissue damage and impaired renal hemodynamic, excretory, and urine-concentrating functions. These alterations were accompanied by significant increases in plasma creatinine, urea, K⁺, H⁺, osmolality, as well as elevated plasma MDA and NO metabolites, ultimately leading to ALI. Notably, FTY-720 pretreatment markedly attenuated AKI, reduced the accumulation of plasma markers, and prevented the development of ALI in the ischemia model. Bilateral nephrectomy also induced profound elevations in plasma creatinine, urea, K⁺, H⁺, and osmolality after 24 h; however, there was no difference in ALI severity between untreated and FTY-720-treated animals in this model of AKI. FTY-720 induced lymphopenia in BNX + FTY and BIR + FTY groups, but only mitigated ischemic AKI and ALI together in the BIR + FTY group. Therefore, lymphocytes are unlikely to mediate directly the link between AKI and ALI.